Crystal Structure of Human Survivin Reveals a Bow Tie?Shaped Dimer with Two Unusual ?-Helical Extensions

Abstract Survivin is a mitotic spindle-associated protein involved in linking mitotic spindle function to activation of apoptosis in mammalian cells. The structure of the full-length human survivin has been determined by X-ray crystallography to 2.7 A. Strikingly, the structure forms a very unusual bow tie–shaped dimer. It does not dimerize through a C-terminal coiled-coil, contrary to sequence analysis prediction. The C-terminal helices contain hydrophobic clusters with the potential for protein–protein interactions. The unusual shape and dimensions of survivin suggest it serves an adaptor function through its α-helical extensions.

[1]  D. Altieri,et al.  A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma , 1997, Nature Medicine.

[2]  C. Sander,et al.  Dali: a network tool for protein structure comparison. , 1995, Trends in biochemical sciences.

[3]  S. Pollefeyt,et al.  Three differentially expressed survivin cDNA variants encode proteins with distinct antiapoptotic functions. , 2000, Blood.

[4]  Fengzhi Li,et al.  Control of apoptosis and mitotic spindle checkpoint by survivin , 1998, Nature.

[5]  C Chothia,et al.  Surface, subunit interfaces and interior of oligomeric proteins. , 1988, Journal of molecular biology.

[6]  Fengzhi Li,et al.  Pleiotropic cell-division defects and apoptosis induced by interference with survivin function , 1999, Nature Cell Biology.

[7]  A. Fraser,et al.  Caenorhabditis elegans inhibitor of apoptosis protein (IAP) homologue BIR-1 plays a conserved role in cytokinesis , 1999, Current Biology.

[8]  Emad S. Alnemri,et al.  Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1 , 1999, Nature.

[9]  A. Brunger.  Free R value: a novel statistical quantity for assessing the accuracy of crystal structures. , 1992 .

[10]  D. Vaux,et al.  Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat , 1999, Nature Structural Biology.

[11]  K Cowtan,et al.  Miscellaneous algorithms for density modification. , 1998, Acta crystallographica. Section D, Biological crystallography.

[12]  J C Reed,et al.  IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. , 1998, Cancer research.

[13]  S. Muchmore,et al.  Crystal structure and mutagenic analysis of the inhibitor-of-apoptosis protein survivin. , 2000, Molecular cell.

[14]  B. Matthews.  Solvent content of protein crystals. , 1968, Journal of molecular biology.

[15]  Stephen W. Fesik,et al.  NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP , 1999, Nature.

[16]  H. Dohlman,et al.  Cell Division Regulation by BIR1, a Member of the Inhibitor of Apoptosis Family in Yeast* , 2000, The Journal of Biological Chemistry.

[17]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[18]  D. Altieri,et al.  Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. , 1998, Cancer research.

[19]  J. Zou,et al.  Improved methods for building protein models in electron density maps and the location of errors in these models. , 1991, Acta crystallographica. Section A, Foundations of crystallography.

[20]  G. Sirugo,et al.  Induction of Apoptosis and Inhibition of Cell Proliferation bysurvivin Gene Targeting* , 1998, The Journal of Biological Chemistry.

[21]  J. Mackay,et al.  Zinc fingers are sticking together. , 1998, Trends in biochemical sciences.

[22]  H. Yoon,et al.  Participation of Bir1p, a member of the inhibitor of apoptosis family, in yeast chromosome segregation events. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Y. Lazebnik,et al.  Crystal structure of Apaf-1 caspase recruitment domain: an alpha-helical Greek key fold for apoptotic signaling. , 1999, Journal of molecular biology.

[24]  J C Reed,et al.  IAP family proteins--suppressors of apoptosis. , 1999, Genes & development.

[25]  R J Read,et al.  Crystallography & NMR system: A new software suite for macromolecular structure determination. , 1998, Acta crystallographica. Section D, Biological crystallography.

[26]  H. Steller,et al.  Deterin, a New Inhibitor of Apoptosis from Drosophila melanogaster * , 2000, The Journal of Biological Chemistry.

[27]  Z. Otwinowski,et al.  [20] Processing of X-ray diffraction data collected in oscillation mode. , 1997, Methods in enzymology.

[28]  Collaborative Computational,et al.  The CCP4 suite: programs for protein crystallography. , 1994, Acta crystallographica. Section D, Biological crystallography.

[29]  R van Driel,et al.  Role for yeast inhibitor of apoptosis (IAP)-like proteins in cell division. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[30]  M. Hatano,et al.  Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[31]  W A Hendrickson,et al.  Selenomethionyl proteins produced for analysis by multiwavelength anomalous diffraction (MAD): a vehicle for direct determination of three‐dimensional structure. , 1990, The EMBO journal.

[32]  E. Chambaz,et al.  Crystal structure of the human protein kinase CK2 regulatory subunit reveals its zinc finger‐mediated dimerization , 1999, The EMBO journal.